The present invention relates generally to an apparatus and method for minimizing the effects of ischemia and the subsequent injury upon reperfusion of organs and/or tissue masses resulting from minimal to total obstructions of normal blood flow. This is achieved by the integration of a pump, heat exchanger and control unit providing the ability to locally cool a part of the anatomy inducing local hypothermia and minimizing and/or eliminating the injury associated with ischemia and subsequent reperfusion.
When a patient comes into the emergency room showing signs of a stroke or heart attack, three options for treatment are available: pharmacological intervention (i.e., the use of thrombolytics), invasive surgery or minimally invasive treatment to eliminate or lessen an obstruction in a coronary vessel. Catheter based treatments have become the standard care path for the diagnosis and treatment of strokes or acute myocardial infarction (AMI). Studies have shown that a significant amount of tissue damage occurs due to the reperfusion of warm blood into the previously occluded vessels.
The total extent of tissue injury and the amount attributed to either the ischemic event or reperfusion is unknown. However, localized cooling has been shown to both reduce tissue injury during ischemia and the amount of injury resulting from reperfusion of the tissue. Reperfusion injury is caused by an immediate increase in rapid flow of blood into an organ or tissue mass previously rendered ischemic and is attributed to oxidative stress, intercellular calcium overload, neutrophil and platelet activation, reduced microvascular flow, metabolic disturbances, the buildup of toxins in the tissue and inflammatory reactions. Renewed normothermic blood flow worsens tissue damage either by causing additional injury or by unmasking injury sustained during the ischemic period. Thus, early treatment of an obstruction, for example in the heart using percutaneous coronary intervention, is desirable. Once the obstruction is alleviated normothermic blood flow is restored to the ischemic region resulting in a reperfusion injury.
Experimental evidence has shown that reductions in tissue temperature can reduce the effects of ischemia, reperfusion injury, or inadequate blood flow. Among other mechanisms, hypothermia decreases tissue metabolism, concentrations of toxic metabolic byproducts, and suppresses the inflammatory response in the aftermath of ischemic tissue injury. Mild cooling of the tissue region by a temperature of as little as 3-4° C. below normal body temperature may provide a protective effect with the increase in protection/reduction in injury directly associated with the decrease in temperature of the organ or tissue effected by the ischemic event. Hypothermia has been shown to drastically reduce oxygen free radical production and intercellular calcium overload, platelet aggregation, the occurrence of microvascular obstruction, metabolic demand, and inflammatory response in the aftermath of ischemic tissue injury. Hypothermia may provide ischemic protection and may enhance patient recovery by ameliorating secondary tissue injury. Depending on the time of initiation, hypothermia can be intra-ischemic, post-ischemic, or both. Hypothermic ischemic protection is preventive if tissue metabolism can be reduced. It may also enhance recovery by reducing secondary tissue injury or decreasing ischemic edema formation. Since the metabolic reduction is less than 10% per degree Celsius, deep hypothermia targeting 20-25 degrees Celsius, provides adequate tissue protection via metabolic slowdown. Secondary tissue injury, thought to be mainly caused by enzymatic activity, is greatly diminished by mild to moderate hypothermia targeting 32-35 degrees Celsius.
Not only can hypothermia be protective for the unexpected onset of ischemia it can be used prophylactically where surgical intervention/medical therapy will cause a known ischemic event (e.g., cardiac bypass and organ transplant surgery). To harness the therapeutic value of hypothermia the primary focus thus far has been on systemic body surface or vascular cooling. Systemic cooling has specific limitations and drawbacks related to its inherent unselective nature. Research has shown that systemic or whole body cooling may lead to cardiovascular irregularities such as reduced cardiac output and ventricular fibrillation, an increased risk of infection, and blood chemistry alterations.
In practice, systemic cooling apparatus and their associated methods require long periods of time to achieve target tissue temperatures causing damage along the way. External cooling devices have been used as adjunct therapy for cardiac arrest where the goal is to salvage brain tissue and improve neurological outcomes. Many systemic cooling systems require the movement of large volumes of blood flow to the brain and cooling is achieved by diluting blood with infusion of cold fluids. In general, these devices and their associated methods are not applicable to localized cooling to reduce reperfusion injury in specific organs or tissue masses. To date localized cooling techniques have been defined by placement of an ice pack over the particular area of a patient's body and puncturing the pericardium and infusing cooled fluid into a reservoir inserted into the pericardial space near the ischemic cardiac tissue.
Few concepts have attempted local, organ specific cooling. Local cooling approaches have been limited by the technological challenges related to developing catheter systems including internal heat exchangers and the reliability and safety associated with their use. Namely, without a control feedback loop monitoring physiological conditions at the treatment location and adjusting the cooling the ability to repeatedly and continually induce specific localized cooling parameters is random at best and lacks the accuracy and repeatability required in providing medical treatment. An advantage of local or organ level cooling is the reduced thermal inertia, since the cooling capacity required is directly proportional to the mass being cooled. Cooling a portion of a 300 gram heart vs. a 70,000 gram body of a patient takes significantly less cooling capacity to reach equivalent reduced temperatures.
While hypothermia technologies have been progressing, the fields of endovascular intervention and minimally invasive surgery have also grown. Today therapeutic devices include stent placement, angioplasty, direct thrombolytic infusion, and mechanical devices for clot removal. In each of these therapeutic environments, ischemic damage is the focus. To accomplish this however, requires an integrated cooling system that not only offers the ability to cool but also can monitor physiological conditions at a specific location in the body. Monitoring the physiological conditions facilitates local cooling of an organ or tissue mass by accommodating heat loss along the length of a catheter, regulating local pressure changes, and provide a sustained environment while adjunct therapy is administered and normal blood flow is restored. Heat transfer enhancement is the fundamental task for achieving safe, effective arterial cooling. Monitoring the conditions at the specific cooling site permits the system to achieve the highest level of cooling capacity in the smallest volume possible. Heat exchanger design optimization attempts to achieve one or a combination of the following objectives: 1) reduce the size of the transport device; 2) increase the UA (U, the overall transport coefficient and A, the exchange surface area) to reduce the device-body fluid driving potential for exchange or increase the heat and or mass exchange rate; and 3) reduce the pumping power required to meet a heat and/or mass exchange target value.
Most endovascular cooling catheter designs employ external passive transport enhancement techniques, where a fixed or static cooling catheter is placed inside a stagnant or moving body fluid. Passive techniques are transport enhancement approaches that do not add mixing energy to the fluid system of interest. The approach involves adding surface area and/or inducing turbulence adjacent to the effective exchange surface area. They are particularly effective when fluid pumping power is virtually limitless. In the human body, however, physiological constraints limit the hydraulic energy or fluid pumping power. As a result, passively enhanced devices in small arterial vessels are likely lead to substantial blood side flow resistance, diminishing organ perfusion levels.
In general, current designs are suited for the venous system, a system with large veins, significantly larger than small arteries. In this environment most of devices have low heat exchange surface area to device volume ratios. This leads to potentially harmful vessel occlusion characteristics, particularly with smaller arterial blood vessels, increasing the chance of further ischemic injury. Unless additional energy is put into the blood flow stream, conservation of energy dictates that in most cases a boost in heat transfer will come at an increased cost in pressure drop. If the cardiovascular system cannot overcome this additional foreign resistance, perfusion rates must fall.
Furthermore traditional catheters do not have dedicated adjunctive therapy pathways. Again, the catheter designs are built largely for the venous applications where adjunctive therapies are less likely. As a result, these designs do not integrate well with existing endovascular tools, such as angioplasty catheters. Although present devices are functional for venous applications, they are not sufficient for arterial applications. Accordingly, a system and method are needed to address the shortfalls of present technology and to provide other new and innovative features.
United States Patent Application Publication No. 2006/0041217 to Halperin discloses the use of a controller applying an algorithm to maintain a predefined infusion pressure, however the controller is limited to systemic pressure alone and does not provided feedback of the local environment where the ischemic event and reperfusion have occurred. Hence the Halperin disclosure does not control the safe application of cooled fluid within the body inducing localized hypothermia.
However, taking blood from the body cooling it and redelivering it within a specific location with control feedback and localized monitoring used in conjunction with interventional devices (stents, angioplasty balloons, etc.) provides a safe and effective means of inducing localized hypothermia to minimize the negative effects associated with temporary ischemia and injury upon reperfusion in a controlled manner.
There are several designs available for a small artery cooling catheter, such as shown in U.S. Patent Application Publication No. 2006-0058859 A1 to Merrill, which is herein incorporated by reference. Some catheter configurations define an exchange catheter with heat and mass exchange surfaces, some define a transport catheter to carry the coolant, and some include a rear external hub to connect the device to an outside control console and engage adjunctive therapeutic devices. One particular cooling catheter configuration uses natural pressure differences between the aorta and the end organ to carry blood inside the cooling catheter.
Traditional devices as taught in U.S. Pat. No. 6,033,383 to Ginsburg and U.S. Pat. No. 6,645,234 to Evans cool blood as a function of heat transfer from a coolant which is delivered within a catheter and provided in close contact with the flowing blood. In other words the blood is cooled as it flows past and/or through a catheter based device having a cooling element contained within its construction. These types of devices do not provide sufficient control so that the specific organ or tissue mass is cooled sufficiently to produce localized hypothermia. Additionally, the multi-lumen designs of Ginsburg and Evans required to provide paths for coolant, blood, and any interventional procedures results in a large external diameter of roughly 8 French. In addition, the pressure differential provided by the normal circulation of blood may not be sufficient to direct flowing blood in a manner required to optimize heat transfer and induce localized hypothermia.
Conversely, a completely external cooling system with sufficient controls and feedback is better able to integrate into the current treatment modality for ischemic conditions (e.g., stents, balloon angioplasty, clot removal devices) and the subsequent reperfusion. United States Patent Application US 2004/0167467 to Harrison et al. discloses a localized cooling method containing a temperature probe within the distal end of the catheter measuring the temperature of the fluid exiting the catheter. However, the temperature probe is not operatively connected to the heat exchanger, and there is no control unit monitoring and adjusting the flow rate, amount of cooling, or the localized pressure to provide a safe and efficacious supply of localized cooled fluid controlled per the users specifications before, prior to, and after an ischemic event.
Accordingly, it would be advantageous to provide an apparatus to facilitate the localized cooling of a flow of blood to a specific region or organ of a patient's body as an adjunct to interventional therapy lessening reperfusion injury, and which is configured with a feedback control system to monitor and adjust both the temperature and pressure of the cooling flow of blood and to monitor the patient's internal temperatures and blood pressures to ensure patient safety.
It would further be advantageous to provide a cooling system capable of delivering cold blood to a treatment site while allowing a physician to use familiar catheters and interventional tools.